What is the clinical evidence from this study?

Study design: Other. Population: Hypertension. Intervention: L-NAME vs. plain tap water. Primary outcome: Expression of Gi alpha protein and associated adenylyl cyclase activity.

What does this research mean for the field?

In rats with L-NAME-induced hypertension but no cardiac hypertrophy, the expression of Gi alpha proteins is significantly enhanced while Gs alpha protein levels remain unaltered, suggesting that previously observed Gs alpha increases in hypertension models are likely due to hypertrophy rather than elevated blood pressure alone. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

August 1, 2000

Enhanced expression of Gi proteins in non-hypertrophic hearts from rats with hypertension-induced by L-NAME treatment

Key Result

L-NAME-induced hypertension in rats (systolic blood pressure 190 vs 121 mmHg) without cardiac hypertrophy resulted in enhanced expression of Gi alpha protein and associated adenylyl cyclase activity.

PICO

Population

Hypertension

Intervention / Comparator

L-NAME vs plain tap water (oral administration in drinking tap water)

Primary Outcome

Expression of Gi alpha protein and associated adenylyl cyclase activity

Abstract

OBJECTIVE: The objective of the present studies is to investigate if the enhanced expression of Gs alpha protein and their mRNA observed in various models of hypertensive rats is due to the expressed hypertrophy or hypertension. METHODS: Hypertension, in Sprague-Dawley rats was induced by the oral administration of the arginine analog N(omega)-nitro-L-arginine methyl ester (L-NAME) in their drinking tap water for a period of 4 weeks. The control rats were given plain tap water only. The levels of inhibitory guanine nucleotide regulatory proteins (Gi alpha-2, Gi alpha-3), stimulatory guanine nucleotide proteins (Gs alpha) and G beta proteins were determined by immunoblotting, whereas the levels of Gi alpha-2, Gi alpha-3, Gs alpha and adenylyl cyclase type V enzyme mRNA were determined by Northern-blotting techniques. Adenylyl cyclase activity was determined by measuring 32PcAMP formation from alpha32PATP. RESULTS: The systolic blood pressure was enhanced in L-NAME-treated rats compared to control rats (190 +/- 9.2 mmHg versus 121 +/- 6.3 mmHg); however, heart-to-body-weight ratio was not different in two groups. The levels of Gi alpha-2 and Gi alpha-3 proteins and their mRNA were significantly augmented in hearts from L-NAME-treated rats, however, the levels of Gs alpha and G beta were unaltered. In addition, the effect of low concentrations of GTPgammaS on forskolin (FSK)-stimulated adenylyl cyclase activity (receptor-independent functions of Gi alpha) was significantly enhanced in L-NAME-treated rats. However, the inhibitions of adenylyl cyclase exerted by oxotremorine, C-ANP(4-23) and angiotensin II (AII) (receptor-dependent function of Gi alpha) were completely attenuated in L-NAME-treated rats. On the other hand, cholera toxin stimulated GTP or GTPgammaS-sensitive adenylyl cyclase activity (Gs alpha function) to similar extent in control and L-NAME-treated rats, suggesting that Gs alpha functions were not altered by L-NAME treatment. However, the stimulatory effects of isoproterenol, glucagon, NaF on adenylyl cyclase were diminished in L-NAME-treated rats. In addition, FSK-stimulated enzyme activity was also diminished in L-NAME-treated rats without any changes in the mRNA levels of type V enzyme. CONCLUSIONS: These results suggest that L-NAME hypertensive rats that do not express cardiac hypertrophy exhibit enhanced expression of Gi alpha protein and associated adenylyl cyclase activity.

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